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1.
Estimation of Fitness Components in DROSOPHILA MELANOGASTER . I. Heterozygote Viability Indices 总被引:2,自引:2,他引:0
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We examine the assumption of "dominance" with regard to viability of the Cy and Pm marker chromosomes in D. melanogaster . This assumption is often invoked for the extraction of wild-type second chromosomes from natural populations and for the calculation of relative viability indices. Significant genotypic variances for viability are found among both Cy/+j and Pm/+i heterozygotes in California and Japanese populations. The magnitude of the Pm/+ i genotypic variance is substantially less than that of the Cy/+j heterozygotes (less than one half). Significant reciprocal effects are also found to influence Cy/+j, Pm/+i and +i/+j viabilities. We conclude that viability indices of heterozygotes based on the Curly method are biased. We suggest that viability indices in the future be expressed relative to the viability of the Cy/Pm genotype (Curly-Plum method) or possibly that of the Pm/+i genotype (Plum method). 相似文献
2.
Hsien Ming Easlon Krishna S. Nemali James H. Richards David T. Hanson Thomas E. Juenger John K. McKay 《Photosynthesis research》2014,119(1-2):119-129
Ecologists and physiologists have documented extensive variation in water use efficiency (WUE) in Arabidopsis thaliana, as well as association of WUE with climatic variation. Here, we demonstrate correlations of whole-plant transpiration efficiency and carbon isotope composition (δ13C) among life history classes of A. thaliana. We also use a whole-plant cuvette to examine patterns of co-variation in component traits of WUE and δ13C. We find that stomatal conductance (g s) explains more variation in WUE than does A. Overall, there was a strong genetic correlation between A and g s, consistent with selection acting on the ratio of these traits. At a more detailed level, genetic variation in A was due to underlying variation in both maximal rate of carboxylation (V cmax) and maximum electron transport rate (Jmax). We also found strong effects of leaf anatomy, where lines with lower WUE had higher leaf water content (LWC) and specific leaf area (SLA), suggesting a role for mesophyll conductance (g m) in variation of WUE. We hypothesize that this is due to an effect through g m, and test this hypothesis using the abi4 mutant. We show that mutants of ABI4 have higher SLA, LWC, and g m than wild-type, consistent with variation in leaf anatomy causing variation in g m and δ13C. These functional data also add further support to the central, integrative role of ABI4 in simultaneously altering ABA sensitivity, sugar signaling, and CO2 assimilation. Together our results highlight the need for a more holistic approach in functional studies, both for more accurate annotation of gene function and to understand co-limitations to plant growth and productivity. 相似文献
3.
Immune cells kill invading microbes by producing reactive oxygen and nitrogen species, primarily hydrogen peroxide (H2O2) and nitric oxide (NO). We previously found that NO inhibits catalases in Escherichia coli, stabilizing H2O2 around treated cells and promoting catastrophic chromosome fragmentation via continuous Fenton reactions generating hydroxyl radicals. Indeed, H2O2-alone treatment kills catalase-deficient (katEG) mutants similar to H2O2+NO treatment. However, the Fenton reaction, in addition to H2O2, requires Fe(II), which H2O2 excess instantly converts into Fenton-inert Fe(III). For continuous Fenton when H2O2 is stable, a supply of reduced iron becomes necessary. We show here that this supply is ensured by Fe(II) recruitment from ferritins and Fe(III) reduction by flavin reductase. Our observations also concur with NO-mediated respiration inhibition that drives Fe(III) reduction. We modeled this NO-mediated inhibition via inactivation of ndh and nuo respiratory enzymes responsible for the step of NADH oxidation, which results in increased NADH pools driving flavin reduction. We found that, like the katEG mutant, the ndh nuo double mutant is similarly sensitive to H2O2-alone and H2O2+NO treatments. Moreover, the quadruple katEG ndh nuo mutant lacking both catalases and efficient respiration was rapidly killed by H2O2-alone, but this killing was delayed by NO, rather than potentiated by it. Taken together, we conclude that NO boosts the levels of both H2O2 and Fe(II) Fenton reactants, making continuous hydroxyl-radical production feasible and resulting in irreparable oxidative damage to the chromosome. 相似文献
4.
We study the effect of human circulation and host/vector heterogeneities on the onset of epidemics of arboviruses. From a meta-population dynamics based on the classical Bailey–Dietz model, we derive a multi-group model under three assumptions: (i) fast host sojourn time-scale; (ii) mosquitoes do not move; (iii) time homogeneity and strong connectivity of human circulation. Within this modelling framework, three different kinds of R0 appear: (i) the “true” or “global” R0—derived from the corresponding next generation matrix; (ii) the uniform R0—obtained if the patches are taken homogeneous; (iii) the local R0s—obtained if the patches are disconnected. We show that there is relevant epidemiological information associated to all of them. In particular, they can be used to understand the effects of changing the circulation on the value of the global R0. We also present additional results on the effects on R0 of different vector control policies, and a simulation with data from the city of Rio de Janeiro, Brazil. 相似文献
5.
N. V. Oreshkova T. S. Sedel’nikova A. V. Pimenov S. P. Efremov 《Russian Journal of Genetics》2014,50(9):934-941
We evaluated the population structure of the bog and dry land populations of the Siberian pine Pinus sibirica (P. sibrica) in Western Siberia using nuclear genome markers. Six pairs of nuclear microsatellite loci were used for this analysis. We detected 30 allelic variants in 120 individuals of four populations of P. sibirica. We established that the studied populations differ by genetic structure. The most essential differences were identified between the Siberian pine population from oligotrophic bog and the group of populations from dry land within eutrophic bogs and near settlements P. sibirica forest (F ST = 0.019; D N = 0.053). We estimated that diversification of the West Siberian populations of P. sibirica exceeded 2.4% (F ST = 0.024), based on an analysis of SSR markers. 相似文献
6.
María Isabel Niemeyer L. Pablo Cid Gaspar Pe?a-Münzenmayer Francisco V. Sepúlveda 《The Journal of biological chemistry》2010,285(22):16467-16475
TASK-2 (KCNK5 or K2P5.1) is a background K+ channel that is opened by extracellular alkalinization and plays a role in renal bicarbonate reabsorption and central chemoreception. Here, we demonstrate that in addition to its regulation by extracellular protons (pHo) TASK-2 is gated open by intracellular alkalinization. The following pieces of evidence suggest that the gating process controlled by intracellular pH (pHi) is independent from that under the command of pHo. It was not possible to overcome closure by extracellular acidification by means of intracellular alkalinization. The mutant TASK-2-R224A that lacks sensitivity to pHo had normal pHi-dependent gating. Increasing extracellular K+ concentration acid shifts pHo activity curve of TASK-2 yet did not affect pHi gating of TASK-2. pHo modulation of TASK-2 is voltage-dependent, whereas pHi gating was not altered by membrane potential. These results suggest that pHo, which controls a selectivity filter external gate, and pHi act at different gating processes to open and close TASK-2 channels. We speculate that pHi regulates an inner gate. We demonstrate that neutralization of a lysine residue (Lys245) located at the C-terminal end of transmembrane domain 4 by mutation to alanine abolishes gating by pHi. We postulate that this lysine acts as an intracellular pH sensor as its mutation to histidine acid-shifts the pHi-dependence curve of TASK-2 as expected from its lower pKa. We conclude that intracellular pH, together with pHo, is a critical determinant of TASK-2 activity and therefore of its physiological function. 相似文献
7.
Habitat change affects both taxonomic and functional biodiversity, and beta-diversity is often used as a metric to describe these changes. Furthermore, spatially closer communities tend to have more similar species compositions (lower beta-diversity). These changes in community composition can be revealed with taxonomic and functional aspects of diversity. We assessed the responses of ant taxonomic and functional beta-diversity to changes in forest cover and spatial distance. We expected that changes in taxonomic and functional beta-diversity along a forest cover gradient would be caused by the replacement of open-habitat ant species by forest-habitat ant species. We sampled ants within twelve landscapes with different forest cover percentages in the southwestern Amazon of Brazil. Both taxonomic and functional beta-diversity of pairwise samples (βBC) were partitioned into their turnover (βBal) and nestedness (βGra) components. Increasing forest cover correlated with increases in taxonomic and functional βBC, however, βBal had a greater contribution to taxonomic βBC and βGra to functional βBC. Taxonomic βBC and βBal and functional βBal increased with spatial distance. Forest-habitat species richness increased, and open-habitat species richness decreased with increasing forest cover, while the richness of habitat-use generalist species did not vary. The loss of environmental heterogeneity may be responsible for generalist species dominance and open-habitat species presence in less-forested landscapes. This leads to great taxonomic replacement, but a nestedness gradient of function. Better land use planning is needed to ensure biodiversity and ecosystem functions of forest habitats in human-modified landscapes. 相似文献
8.
Neisseria gonorrhoeae is a microaerophile that, when oxygen availability is limited, supplements aerobic respiration with a truncated denitrification pathway, nitrite reduction to nitrous oxide. We demonstrate that the cccA gene of Neisseria gonorrhoeae strain F62 (accession number NG0292) is expressed, but the product, cytochrome c2, accumulates to only low levels. Nevertheless, a cccA mutant reduced nitrite at about half the rate of the parent strain. We previously reported that cytochromes c4 and c5 transfer electrons to cytochrome oxidase cbb3 by two independent pathways and that the CcoP subunit of cytochrome oxidase cbb3 transfers electrons to nitrite. We show that mutants defective in either cytochrome c4 or c5 also reduce nitrite more slowly than the parent. By combining mutations in cccA (Δc2), cycA (Δc4), cycB (Δc5), and ccoP (ccoP-C368A), we demonstrate that cytochrome c2 is required for electron transfer from cytochrome c4 via the third heme group of CcoP to the nitrite reductase, AniA, and that cytochrome c5 transfers electrons to nitrite reductase by an independent pathway. We propose that cytochrome c2 forms a complex with cytochrome oxidase. If so, the redox state of cytochrome c2 might regulate electron transfer to nitrite or oxygen. However, our data are more consistent with a mechanism in which cytochrome c2 and the CcoQ subunit of cytochrome oxidase form alternative complexes that preferentially catalyze nitrite and oxygen reduction, respectively. Comparison with the much simpler electron transfer pathway for nitrite reduction in the meningococcus provides fascinating insights into niche adaptation within the pathogenic neisseriae. 相似文献
9.
The genus Flaveria consists of 23 species with significant variation in photosynthetic physiologies. We tested whether photosynthetic pathway variation in seven co-existing Flaveria species corresponds to geographic distributions or physiological performance in C3, C4, and intermediate species growing under natural conditions in south-central Mexico. We found that Flaveria pringlei (C3) was the most widely distributed species with multiple growth habits. Numerous populations of Flaveria kochiana (C4), a recently described species with a previously unknown distribution, were located in the Mixtec region of Oaxaca. Flaveria cronquistii (C3) and Flaveria ramosissima (C3-C4) were only located in the Tehuacán Valley region while Flaveria trinervia (C4) was widely distributed. Only one population of Flaveria angustifolia (C3-C4) and Flaveria vaginata (C4-like) were located near Izúcar de Matamoros. Midday leaf water potential differed significantly between Flaveria species, but did not vary according to growth habit or photosynthetic pathway. The quantum yield of photosystem II did not vary between species, despite large differences in leaf nitrogen content, leaf shape, plant size and life histories. We did not find a direct relationship between increasing C4 cycle characteristics and physiological performance in the Flaveria populations examined. Furthermore, C3 species were not found at higher elevation than C4 species as expected. Our observations indicate that life history traits and disturbance regime may be the primary controllers of Flaveria distributions in south-central Mexico. 相似文献
10.
O. A. Kovaleva A. K. Shchyolkina O. K. Mamaeva V. A. Ol’shevskaya A. V. Makarenkov A. S. Semeikin A. A. Shtil O. F. Borisova D. N. Kaluzhny 《Molecular Biology》2013,47(3):453-460
Porphyrins are a chemical class that is widely used in drug design. Cationic porphyrins may bind to DNA guanine quadruplexes. We report the parameters of the binding of 5,10,15,20-tetrakis(N-carboxymethyl-4-pyridinium) porphyrin (P1) and 5,10,15,20-tetrakis(N-etoxycarbonylmethyl-4-pyridinium) porphyrin (P2) to antiparallel telomeric G-quadruplex formed by d(TTAGGG)4 sequence (TelQ). The binding constants (K i ) and the number of binding sites (N j ) were determined from absorption isotherms generated from the absorption spectra of complexes of P1 and P2 with TelQ. Compound P1 demonstrated a high affinity to TelQ (K i = (40 ± 6) × 106 M?1, N 1 = 1; K 2 = (5.4 ± 0.4) × 106 M?1, N 2 = 2). In contrast, the binding constants of P2-TelQ complexes (K 1 = (3.1 ± 0.2) × 106 M?1, N 1 = 1; K 2 = (1.2 ± 0.2) × 106 M?1, N 2 = 2) were one order of magnitude smaller than the corresponding values for P2-TelQ complexes. Measurements of the quantum yield and fluorescence lifetime of the drug’s TelQ complexes revealed two types of binding sites for P1 and P2 on the quadruplex oligonucleotide. We concluded that strong complexes can result from the interaction of the porphyrins with TTA loops whereas the weaker complexes are formed with G-quartets. The altered TelQ conformation detected by the circular dichroism spectra of P1-TelQ complexes can be explained by the disruption of the G-quartet. We conclude that peripheral carboxy groups contribute to the high affinity of P1 for the antiparallel telomeric G-quadruplex. 相似文献
11.
Nina N. Kudryashova Ivan V. Kazbanov Alexander V. Panfilov Konstantin I. Agladze 《PloS one》2015,10(11)
Waveblock formation is the main cause of reentry. We have performed a comprehensive numerical modeling study of block formation due to anisotropy in Ten Tusscher and Panfilov (2006) ionic model for human ventricular tissue. We have examined the border between different areas of myocardial fiber alignment and have shown that blockage can occur for a wave traveling from a transverse fiber area to a longitudinal one. Such blockage occurs for reasonable values of the anisotropy ratio (AR): from 2.4 to 6.2 with respect to propagation velocities. This critical AR decreases by the suppression of I
Na and I
Ca, slightly decreases by the suppression of I
Kr and I
Ks, and substantially increases by the suppression of I
K1. Hyperkalemia affects the block formation in a complex, biphasic way. We provide examples of reentry formation due to the studied effects and have concluded that the suppression of I
K1 should be the most effective way to prevent waveblock at the areas of abrupt change in anisotropy. 相似文献
12.
Background and aims
Elevated atmospheric CO2 (eCO2) and tropospheric O3 (eO3) can alter soil microbial processes, including those underlying N2O emissions, as an indirect result of changes in plant inputs. In this study, effects of eCO2 and eO3 on sources of N2O in a soybean (Glycine max (L.) Merr.) agroecosystem in Illinois (SoyFACE) were investigated. We hypothesized that increases in available C and anaerobic microhabitat under eCO2 would stimulate N2O emissions, with a proportionally larger increase in denitrification derived N2O (N2OD) compared to nitrification plus nitrifier denitrification derived N2O (N2ON+ND). We expected opposite effects under eO3.Methods
Isotopically labeled 15NH 4 14 NO3 and 14NH 4 15 NO3 were used to evaluate mineral N transformations, N2OD, and N2ON+ND in a 12-day incubation experiment.Results
We observed minimal effects of eCO2 and eO3 on N2O emissions, movement of 15?N through mineral N pools, soil moisture content and C availability. Possibly, altered C and N inputs by eCO2 and eO3 were small relative to the high soil organic C content and N-inputs via biological N2-fixation, minimizing potential effects of eCO2 and eO3 on N-cycling.Conclusion
We conclude that eCO2 and eO3 did not affect N2O emissions in the short term. However, it remains to be tested whether N2O emissions in SoyFACE will be unaltered by eCO2 and eO3 on a larger temporal scale under field conditions. 相似文献13.
Ka-Weng Ieong Gabriele Indrisiunaite Arjun Prabhakar Joseph D Puglisi Mns Ehrenberg 《Nucleic acids research》2021,49(5):2684
We used quench flow to study how N6-methylated adenosines (m6A) affect the accuracy ratio between kcat/Km (i.e. association rate constant (ka) times probability (Pp) of product formation after enzyme-substrate complex formation) for cognate and near-cognate substrate for mRNA reading by tRNAs and peptide release factors 1 and 2 (RFs) during translation with purified Escherichia coli components. We estimated kcat/Km for Glu-tRNAGlu, EF-Tu and GTP forming ternary complex (T3) reading cognate (GAA and Gm6AA) or near-cognate (GAU and Gm6AU) codons. ka decreased 10-fold by m6A introduction in cognate and near-cognate cases alike, while Pp for peptidyl transfer remained unaltered in cognate but increased 10-fold in near-cognate case leading to 10-fold amino acid substitution error increase. We estimated kcat/Km for ester bond hydrolysis of P-site bound peptidyl-tRNA by RF2 reading cognate (UAA and Um6AA) and near-cognate (UAG and Um6AG) stop codons to decrease 6-fold or 3-fold by m6A introduction, respectively. This 6-fold effect on UAA reading was also observed in a single-molecule termination assay. Thus, m6A reduces both sense and stop codon reading accuracy by decreasing cognate significantly more than near-cognate kcat/Km, in contrast to most error inducing agents and mutations, which increase near-cognate at unaltered cognate kcat/Km. 相似文献
14.
Sergios A. Nicolaou Alan G. Fast Eiko Nakamaru-Ogiso Eleftherios T. Papoutsakis 《Applied and environmental microbiology》2013,79(23):7210-7219
Reactive oxygen species are generated by redox reactions and the Fenton reaction of H2O2 and iron that generates the hydroxyl radical that causes severe DNA, protein, and lipid damage. We screened Escherichia coli genomic libraries to identify a fragment, containing cueR, ybbJ, qmcA, ybbL, and ybbM, which enhanced resistance to H2O2 stress. We report that the ΔybbL and ΔybbM strains are more susceptible to H2O2 stress than the parent strain and that ybbL and ybbM overexpression overcomes H2O2 sensitivity. The ybbL and ybbM genes are predicted to code for an ATP-binding cassette metal transporter, and we demonstrate that YbbM is a membrane protein. We investigated various metals to identify iron as the likely substrate of this transporter. We propose the gene names fetA and fetB (for Fe transport) and the gene product names FetA and FetB. FetAB allows for increased resistance to oxidative stress in the presence of iron, revealing a role in iron homeostasis. We show that iron overload coupled with H2O2 stress is abrogated by fetA and fetB overexpression in the parent strain and in the Δfur strain, where iron uptake is deregulated. Furthermore, we utilized whole-cell electron paramagnetic resonance to show that intracellular iron levels in the Δfur strain are decreased by 37% by fetA and fetB overexpression. Combined, these findings show that fetA and fetB encode an iron exporter that has a role in enhancing resistance to H2O2-mediated oxidative stress and can minimize oxidative stress under conditions of iron overload and suggest that FetAB facilitates iron homeostasis to decrease oxidative stress. 相似文献
15.
Dixie F. Mollenkopf Jennifer M. Mirecki Joshua B. Daniels Julie A. Funk Steven C. Henry Glenn E. Hansen Peter R. Davies Tara S. Donovan Thomas E. Wittum 《Applied and environmental microbiology》2013,79(3):1052-1054
We report the recovery of Escherichia coli or Klebsiella pneumoniae containing the extended-spectrum β-lactamase gene blaCTX-M from 24 of 1,495 (1.6%) swine fecal samples in 8 of 50 (16%) finishing barns located in 5 U.S. states. We did not detect an association between antimicrobial use and recovery of blaCTX-M. 相似文献
16.
Neusa Martins Maria Leonor Osório Sandra Gonçalves Júlio Osório Anabela Romano 《Biometals》2013,26(3):427-437
We evaluated the impact of low pH and aluminum (Al) on the leaves and roots of Plantago almogravensis Franco and Plantago algarbiensis Samp., focusing on energy partitioning in photosystem II, H2O2 levels, lipid peroxidation, electrolyte leakage (EL), protein oxidation, total soluble protein content and antioxidant enzyme activities. In both species, Al triggered more changes in oxidative metabolism than low pH alone, particularly in the roots. We found that Al increased the levels of H2O2 in P. algarbiensis roots, but reduced the levels of H2O2 in P. almogravensis leaves and roots. Neither low pH nor Al affected the spatial heterogeneity of chlorophyll fluorescence, the maximum photochemical efficiency of PSII (Fv/Fm), the actual quantum efficiency of PSII (?PSII) or the quantum yields of regulated (?NPQ) and nonregulated (?NO) energy dissipation, and there was no significant change in total soluble protein content and EL. In P. algarbiensis, Al increased the carbonyl content and the activities of superoxide dismutase (SOD) and catalase (CAT) in the roots, and also CAT, ascorbate peroxidase and guaiacol peroxidase activities in the leaves. In P. almogravensis, Al reduced the level of malondialdehyde in the roots as well as SOD activity in the leaves and roots. We found that P. almogravensis plantlets could manage the oxidative stress caused by low pH and Al, whereas the P. algarbiensis antioxidant system was unable to suppress Al toxicity completely, leading to the accumulation of H2O2 and consequential protein oxidation in the roots. 相似文献
17.
《Biophysical journal》2020,118(1):57-69
Cell-penetrating peptides (CPPs) can translocate across plasma membranes to enter the cytosol of eukaryotic cells without decreasing cell viability. We revealed the mechanism underlying this translocation by examining the effect of membrane potential, φm, on the entry of a CPP, transportan 10 (TP10), into the lumen of single giant unilamellar vesicles (GUVs). For this purpose, we used the single GUV method to detect the entry of carboxyfluorescein (CF)-labeled TP10 (CF-TP10) into the lumen of single GUVs. First, we used various K+ concentration differences to apply different negative membrane potentials on single GUVs containing gramicidin A in their membrane and confirmed these potentials using the φm-sensitive fluorescent probe 3,3′-dihexyloxacarbocyanine iodine. The fluorescence intensity of the GUV membranes (i.e., the rim intensity) due to 3,3′-dihexyloxacarbocyanine iodine increased with |φm| up to 118 mV, and its dependence on |φm| less than 28 mV agreed with a theoretical estimation (i.e., the dye concentration in the inner leaflet of a GUV is larger than that in the outer leaflet according to the Boltzmann distribution). We then examined the effect of φm on the entry of CF-TP10 into GUVs using single GUVs containing small GUVs or large unilamellar vesicles inside the mother GUV lumen. We found that CF-TP10 entered the GUV lumen without pore formation and the rate of entry of CF-TP10 into the GUV lumen, Ventry, increased with an increase in |φm|. The rim intensity due to CF-TP10 increased with an increase in |φm|, indicating that the CF-TP10 concentration in the inner leaflet of the GUV increased with |φm|. These results indicate that the φm-induced elevation in Ventry can be explained by the increase in CF-TP10 concentration in the inner leaflet with |φm|. We discuss the mechanism underlying this effect of membrane potential based on the pre-pore model of the translocation of CF-TP10 across a GUV membrane. 相似文献
18.
With an ecological-evolutionary perspective increasingly applied toward the conservation and management of endangered or exploited species, the genetic estimation of effective population size (Ne) has proliferated. Based on a comprehensive analysis of empirical literature from the past two decades, we asked: (i) how often do studies link Ne to the adult census population size (N)? (ii) To what extent is Ne correctly linked to N? (iii) How readily is uncertainty accounted for in both Ne and N when quantifying Ne/N ratios? and (iv) how frequently and to what degree might errors in the estimation of Ne or N affect inferences of Ne/N ratios? We found that only 20% of available Ne estimates (508 of 2617; 233 studies) explicitly attempted to link Ne and N; of these, only 31% (160 of 508) correctly linked Ne and N. Moreover, only 7% (41 of 508) of Ne/N ratios (correctly linked or not) reported confidence intervals for both Ne and N; for those cases where confidence intervals were reported for Ne only, 31% of Ne/N ratios overlapped with 1, of which more than half also reached below Ne/N = 0.01. Uncertainty in Ne/N ratios thus sometimes spanned at least two orders of magnitude. We conclude that the estimation of Ne/N ratios in natural populations could be significantly improved, discuss several options for doing so, and briefly outline some future research directions. 相似文献
19.
S?ren D. ?stergaard Shubhabrata Mukherjee Stephen J. Sharp Petroula Proitsi Luca A. Lotta Felix Day John R. B. Perry Kevin L. Boehme Stefan Walter John S. Kauwe Laura E. Gibbons Alzheimer’s Disease Genetics Consortium The GERAD Consortium EPIC-InterAct Consortium Eric B. Larson John F. Powell Claudia Langenberg Paul K. Crane Nicholas J. Wareham Robert A. Scott 《PLoS medicine》2015,12(6)
Background
Potentially modifiable risk factors including obesity, diabetes, hypertension, and smoking are associated with Alzheimer disease (AD) and represent promising targets for intervention. However, the causality of these associations is unclear. We sought to assess the causal nature of these associations using Mendelian randomization (MR).Methods and Findings
We used SNPs associated with each risk factor as instrumental variables in MR analyses. We considered type 2 diabetes (T2D, N SNPs = 49), fasting glucose (N SNPs = 36), insulin resistance (N SNPs = 10), body mass index (BMI, N SNPs = 32), total cholesterol (N SNPs = 73), HDL-cholesterol (N SNPs = 71), LDL-cholesterol (N SNPs = 57), triglycerides (N SNPs = 39), systolic blood pressure (SBP, N SNPs = 24), smoking initiation (N SNPs = 1), smoking quantity (N SNPs = 3), university completion (N SNPs = 2), and years of education (N SNPs = 1). We calculated MR estimates of associations between each exposure and AD risk using an inverse-variance weighted approach, with summary statistics of SNP–AD associations from the International Genomics of Alzheimer’s Project, comprising a total of 17,008 individuals with AD and 37,154 cognitively normal elderly controls. We found that genetically predicted higher SBP was associated with lower AD risk (odds ratio [OR] per standard deviation [15.4 mm Hg] of SBP [95% CI]: 0.75 [0.62–0.91]; p = 3.4 × 10−3). Genetically predicted higher SBP was also associated with a higher probability of taking antihypertensive medication (p = 6.7 × 10−8). Genetically predicted smoking quantity was associated with lower AD risk (OR per ten cigarettes per day [95% CI]: 0.67 [0.51–0.89]; p = 6.5 × 10−3), although we were unable to stratify by smoking history; genetically predicted smoking initiation was not associated with AD risk (OR = 0.70 [0.37, 1.33]; p = 0.28). We saw no evidence of causal associations between glycemic traits, T2D, BMI, or educational attainment and risk of AD (all p > 0.1). Potential limitations of this study include the small proportion of intermediate trait variance explained by genetic variants and other implicit limitations of MR analyses.Conclusions
Inherited lifetime exposure to higher SBP is associated with lower AD risk. These findings suggest that higher blood pressure—or some environmental exposure associated with higher blood pressure, such as use of antihypertensive medications—may reduce AD risk. 相似文献20.
Chun Wang Derrick Y. F. Lai Chuan Tong Weiqi Wang Jiafang Huang Chongsheng Zeng 《PloS one》2015,10(5)
Understanding the functional relationship between greenhouse gas fluxes and environmental variables is crucial for predicting the impacts of wetlands on future climate change in response to various perturbations. We examined the relationships between methane (CH4) emission and temperature in two marsh stands dominated by the Phragmites australis and Cyperus malaccensis, respectively, in a subtropical estuarine wetland in southeast China based on three years of measurement data (2007–2009). We found that the Q10 coefficient of CH4 emission to soil temperature (Qs10) from the two marsh stands varied slightly over the three years (P > 0.05), with a mean value of 3.38 ± 0.46 and 3.89 ± 0.41 for the P. australis and C. malaccensis stands, respectively. On the other hand, the three-year mean Qa10 values (Q10 coefficients of CH4 emission to air temperature) were 3.39 ± 0.59 and 4.68 ± 1.10 for the P. australis and C. malaccensis stands, respectively, with a significantly higher Qa10 value for the C. malaccensis stand in 2008 (P < 0.05). The seasonal variations of Q10 (Qs10 and Qa10) differed among years, with generally higher values in the cold months than those in the warm months in 2007 and 2009. We found that the Qs10 values of both stands were negatively correlated with soil conductivity, but did not obtain any conclusive results about the difference in Q10 of CH4 emission between the two tidal stages (before flooding and after ebbing). There were no significant differences in both Qs10 and Qa10 values of CH4 emission between the P. australis stand and the C. malaccensis stands (P > 0.05). Our results show that the Q10 values of CH4 emission in this estuarine marsh are highly variable across space and time. Given that the overall CH4 flux is governed by a suite of environmental factors, the Q10 values derived from field measurements should only be considered as a semi-empirical parameter for simulating CH4 emissions. 相似文献